This proposed research is to further analyze the fertilizing ability of human spermatozoa. The project is divided into two major areas, clinically related problems of male infertility and basic questions concerning the fertilization process. An in vitro assay using zona-free hamster eggs will be employed for all studies. In the area of clinical research the objectives include extending the fertilization data on fertile and subfertile men, determining the effectiveness of varicocelectomy on improving sperm fertilizing ability, studying the effect of freezing on fertilizing ability, studying the relationship of morphology to fertilizing ability, and testing the effectiveness of some current therapy for male infertility in actually improving fertilization ability. In the area of more basic questions related to fertilization, the timing of fertilization in vitro will be clarified, the role of cAMP and energy sources in fertilization will be studied and the effect of seminal fluid components and trypsin inhibitors on fertilization will be explored. Human spermatozoa will be utilized in all studies in an in vitro fertilization system with swollen sperm heads in the hamster zona-free egg cytoplasm as the end point of fertilization.